Antigen presentation by tumor-associated macrophages drives T cells from a progenitor exhaustion state to terminal exhaustion.

Whereas terminally exhausted T (Tex_term) cells retain anti-tumor cytotoxic functions, the frequencies of stem-like progenitor-exhausted T (Tex_prog) cells better reflect immunotherapeutic responsivity. Here, we examined the intratumoral cellular interactions that govern the transition to terminal T cell exhaustion. We defined a metric reflecting the intratumoral progenitor exhaustion-to-terminal exhaustion ratio (PETER), which decreased with tumor progression in solid cancers.

Patient-derived organoid model of olfactory ensheathing cell tumor.

We developed a culture model of a human olfactory ensheathing cell tumor. Cultured organoids resemble normal ensheathing cells. Assays suggest that this model provides a tool for studying the roles of these glial cells in the maintenance of the peripheral olfactory system.

Long-term olfactory loss post-COVID-19: Pathobiology and potential therapeutic strategies.

An acute loss of smell emerged as a striking symptom present in roughly half of the people infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in the early phases of the COVID-19 pandemic. In most COVID-19 patients, olfaction recovers over the course of a few weeks. However, a lasting partial or complete loss of smell, often associated with distorted olfactory perceptions termed parosmia, has emerged as a widespread problem impacting at least 5%-10% of those who experience anosmia due to COVID-19.

Olfactory neuroblastoma mimics molecular heterogeneity and lineage trajectories of small-cell lung cancer.

The olfactory epithelium undergoes neuronal regeneration from basal stem cells and is susceptible to olfactory neuroblastoma (ONB), a rare tumor of unclear origins. Employing alterations in Rb1/Trp53/Myc (RPM), we establish a genetically engineered mouse model of high-grade metastatic ONB exhibiting a NEUROD1 immature neuronal phenotype. We demonstrate that globose basal cells (GBCs) are a permissive cell of origin for ONB and that ONBs exhibit cell fate heterogeneity that mimics normal GBC developmental trajectories.

Polycomb repressive complex 2 regulates basal cell fate during adult olfactory neurogenesis.

Adult neurogenesis occurs in the mammalian olfactory epithelium to maintain populations of neurons that are vulnerable to injury yet essential for olfaction. Multipotent olfactory basal stem cells are activated by damage, although mechanisms regulating lineage decisions are not understood. Using mouse lesion models, we focused on defining the role of Polycomb repressive complexes (PRCs) in olfactory neurogenesis.

Preparation of Human Olfactory Epithelial Biopsies for Downstream Analysis.

The olfactory mucosa, lining a portion of the nasal cavity, houses the primary olfactory sensory neurons responsible for odor transduction, along with supporting cell populations. Tremendous advances have come from studying the peripheral olfactory system in animal models, especially the mouse. However, acquired human olfactory disorders lack effective therapies, and many of these conditions involve pathology in the olfactory mucosa.

Deconstructing Olfactory Epithelium Developmental Pathways in Olfactory Neuroblastoma.

Unlabelled: Olfactory neuroblastoma is a rare tumor arising from the olfactory cleft region of the nasal cavity. Because of the low incidence of this tumor, as well as an absence of established cell lines and murine models, understanding the mechanisms driving olfactory neuroblastoma pathobiology has been challenging. Here, we sought to apply advances from research on the human olfactory epithelial neurogenic niche, along with new biocomputational approaches, to better understand the cellular and molecular factors in low- and high-grade olfactory neuroblastoma and how specific transcriptomic markers may predict prognosis.

Safety and Feasibility of Steroid-Eluting Stent as a Bolster in Endoscopic Anterior Skull Base Reconstruction.

Background: With a rising incidence of cerebrospinal fluid (CSF) leaks, endoscopic endonasal CSF leak repair is increasingly performed. Current approaches utilize a variety of materials including free mucosal grafts and vascularized flaps, but post-op leaks continue to be reported. Steroid-eluting bioabsorbable stents (SES) are used during functional endoscopic sinus surgery for chronic rhinosinusitis to reduce inflammation and scarring while maintaining patency of sinus ostia.

Olfactory dysfunction and COVID-19.

Here, we provide an overview of olfactory dysfunction associated with COVID-19. We provide background regarding the organization and function of the peripheral olfactory system. A review of the relevant literature on anosmia and parosmia due to infection with SARS-CoV-2, the virus causing COVID-19, is provided.

Persistent post-COVID-19 smell loss is associated with inflammatory infiltration and altered olfactory epithelial gene expression.

Most human subjects infected by SARS-CoV-2 report an acute alteration in their sense of smell, and more than 25% of COVID patients report lasting olfactory dysfunction. While animal studies and human autopsy tissues have suggested mechanisms underlying acute loss of smell, the pathophysiology that underlies persistent smell loss remains unclear. Here we combine objective measurements of smell loss in patients suffering from post-acute sequelae of SARS-CoV-2 infection (PASC) with single cell sequencing and histology of the olfactory epithelium (OE).

Elevated glucose alters global gene expression and tenascin-C alternative splicing in mesangial cells.

Mesangial cells are the major extracellular matrix (ECM)-producing cells in the kidney glomerulus and, when exposed to elevated glucose levels, they up-regulate assembly of fibronectin (FN) and other ECM proteins. Increases in glucose concentration are known to alter gene expression; here we investigated the connection between increased ECM production and changes in gene expression in mesangial cells. Comparison of mesangial cells grown in normal or high glucose conditions by RNA-sequencing showed significant expression changes in over 6000 genes and, when grouped by KEGG pathway analysis, identified the ECM-receptor interaction and focal adhesion pathways among the top 5 upregulated pathways.

Validation of the Argentine version of the Montreal Cognitive Assessment Test (MOCA): A screening tool for Mild Cognitive Impairment and Mild Dementia in Elderly.

Unlabelled: The MoCA is a brief useful test to diagnose mild cognitive impairment (MCI) and mild dementia (MD). To date, no Argentine cross-cultural adapted validations of the Spanish version have been reported.

Objective: To validate the MoCA in the elderly and study its usefulness in MCI and MD.

Acute Bilateral Superior Branch Vestibular Neuropathy.

The rapid onset of a bilateral vestibular hypofunction (BVH) is often attributed to vestibular ototoxicity. However, without any prior exposure to ototoxins, the idiopathic form of BVH is most common. Although sequential bilateral vestibular neuritis (VN) is described as a cause of BVH, clinical evidence for simultaneous and acute onset bilateral VN is unknown.

Establishing Primary Human Glioblastoma Adherent Cultures from Operative Specimens.

This chapter describes a method for isolation, maintenance, and propagation of primary glioblastoma (GBM) cells in adherent monolayer cultures from patient tumor specimens. This method enables the establishment of GBM cultures with stem or progenitor-like cell characteristics, including self-renewal capacity, differentiation along restricted neural lineages, and tumor-initiating potential when orthotopically injected into immunocompromised mice. This experimentally tractable model system is therefore suitable for a wide variety of analyses in vitro as well as in vivo.

Overall outpatient satisfaction and its components: perceived changes at the Huntington VA Medical Center over five years.

The number of veterans obtaining healthcare services at Huntington Veteran's Administration Medical Center (HVAMC) had significantly increased over the five-year span from fiscal year 2000 through fiscal year 2004. The authors' purpose in this study was to determine changes in outpatient satisfaction levels at HVAMC over that five-year period. The authors assessed the following specific measures of patient satisfaction: courtesy, access, patient preferences, coordination of care, education and information, emotional support, overall quality, pharmacy services, and overall satisfaction.